Article abstract
Nature Chemical Biology 1, 53 - 59 (2005)
Published online: 24 May 2005 | doi:10.1038/nchembio704
A molecular basis for NO selectivity in soluble guanylate cyclase
Elizabeth M Boon1, Shirley H Huang2 & Michael A Marletta1,2,3
Abstract
Soluble guanylate cyclases (sGCs) function as heme sensors that selectively bind nitric oxide (NO), triggering reactions essential to animal physiology. Recent discoveries place sGCs in the H-NOX family (heme nitric oxide/oxygen-binding domain), which includes bacterial proteins from aerobic and anaerobic organisms. Some H-NOX proteins tightly bind oxygen (O2), whereas others show no measurable affinity for O2, providing the basis for selective NO signaling in aerobic cells. Using a series of wild-type and mutant H-NOXs, we established a molecular basis for ligand discrimination. A distal pocket tyrosine is requisite for O2 binding in the H-NOX family. These data suggest that sGC uses a kinetic selection against O2; we propose that the O2 dissociation rate in the absence of this tyrosine is fast and that a stable O2 complex does not form.
- Department of Chemistry, University of California, Berkeley, California 94720, USA.
- Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
- Division of Physical Biosciences, Lawrence Berkeley National Lab, Berkeley, California 94720, USA.
Correspondence to: Michael A Marletta1,2,3 e-mail: marletta@berkeley.edu
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